Liver disease is increasing in incidence, morbidity and mortality because of lack of effective preventative measures and absence of specific treatment. Therapy is largely symptomatic or supportive for fatty liver, hepatitis, cirrhosis, hepatocellular cancer and metabolic disorders which are the common diseases of the liver. The development and monitoring of the effectiveness of specific measures requires objective indices to the repair process--cell replication and fibrosis.
Incubating liver biopsies in Engles' Medium tritiated thymidine at controlled temperature, pH, and oxygen content provide objective evidence of DNA synthesis. Cells incorporating H3T into DNA were evaluated by autoradiographs and counted. It was found that (a) regenerative phases of liver injury account for progressive liver failure in chronic disease, (b) increased DNA can be recognized as the first phase of neoplasia, and (c) correction of folic acid, vitamin B.sub.6, zinc and protein deficiency stimulate DNA synthesis and leads to recovery.
A similar set of circumstances was found when tritiated proline incorporation into collagen was studied. These investigations showed that liver injury, by ethanol and other noxious substances, bile duct proliferation and a fibrogenic lymphokine stimulate collagen synthesis. With elimination of the etiologic factor, early phase fibrosis due to biliary obstruction or alcoholism often disappears.
A protocol for the evaluation of nucleic acid and collagen synthesis capacity of percutaneous liver biopsies is disclosed in Medical Clinics of North America (Volume 63, No.3, May 1979). Such protocol suffered, however, from inadequay of incubation between the biopsies and the tritiated thymidine and tritiated proline as a result of inherent structure of the liver and concomitant liver biopsies, and thus did not provide quantitative results of DNA and collagen synthesis as well as any knowledge of interrelationship between such syntheses.